1h7x
DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL
| |||||||
| , resolution 2.01Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , and | ||||||
| Gene: | DPYD (Sus scrofa) | ||||||
| Activity: | Dihydropyrimidine dehydrogenase (NADP(+)), with EC number 1.3.1.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
Dihydropyrimidine dehydrogenase catalyzes the first step in pyrimidine degradation: the NADPH-dependent reduction of uracil and thymine to the corresponding 5,6-dihydropyrimidines. Its controlled inhibition has become an adjunct target for cancer therapy, since the enzyme is also responsible for the rapid breakdown of the chemotherapeutic drug 5-fluorouracil. The crystal structure of the homodimeric pig liver enzyme (2x 111 kDa) determined at 1.9 A resolution reveals a highly modular subunit organization, consisting of five domains with different folds. Dihydropyrimidine dehydrogenase contains two FAD, two FMN and eight [4Fe-4S] clusters, arranged in two electron transfer chains that pass the dimer interface twice. Two of the Fe-S clusters show a hitherto unobserved coordination involving a glutamine residue. The ternary complex of an inactive mutant of the enzyme with bound NADPH and 5-fluorouracil reveals the architecture of the substrate-binding sites and residues responsible for recognition and binding of the drug.
About this StructureAbout this Structure
1H7X is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil., Dobritzsch D, Schneider G, Schnackerz KD, Lindqvist Y, EMBO J. 2001 Feb 15;20(4):650-60. PMID:11179210
Page seeded by OCA on Thu Mar 20 11:33:29 2008